Michelle Lightfoot1, Lauren Montemorano1, Kristin Bixel2. 1. Ohio State Wexner Medical Center, M210 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH-43210, USA. 2. Ohio State Wexner Medical Center, M210 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH-43210, USA. Kristin.bixel@osumc.edu.
Abstract
PURPOSE OF REVIEW: Conventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy. RECENT FINDINGS: PARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15-30% of women with ovarian cancer will have a germline or somatic BRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand. While the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.
PURPOSE OF REVIEW: Conventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy. RECENT FINDINGS: PARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15-30% of women with ovarian cancer will have a germline or somatic BRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand. While the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.
Authors: Bella Kaufman; Ronnie Shapira-Frommer; Rita K Schmutzler; M William Audeh; Michael Friedlander; Judith Balmaña; Gillian Mitchell; Georgeta Fried; Salomon M Stemmer; Ayala Hubert; Ora Rosengarten; Mariana Steiner; Niklas Loman; Karin Bowen; Anitra Fielding; Susan M Domchek Journal: J Clin Oncol Date: 2014-11-03 Impact factor: 44.544
Authors: Panagiotis A Konstantinopoulos; William T Barry; Michael Birrer; Shannon N Westin; Karen A Cadoo; Geoffrey I Shapiro; Erica L Mayer; Roisin E O'Cearbhaill; Robert L Coleman; Bose Kochupurakkal; Christin Whalen; Jennifer Curtis; Sarah Farooq; Weixiu Luo; Julia Eismann; Mary K Buss; Carol Aghajanian; Gordon B Mills; Sangeetha Palakurthi; Paul Kirschmeier; Joyce Liu; Lewis C Cantley; Scott H Kaufmann; Elizabeth M Swisher; Alan D D'Andrea; Eric Winer; Gerburg M Wulf; Ursula A Matulonis Journal: Lancet Oncol Date: 2019-03-14 Impact factor: 41.316
Authors: Martee L Hensley; Brigitte A Barrette; Klaus Baumann; David Gaffney; Anne L Hamilton; Jae-Weon Kim; Johanna U Maenpaa; Patricia Pautier; Nadeem Ahmad Siddiqui; Anneke M Westermann; Isabelle Ray-Coquard Journal: Int J Gynecol Cancer Date: 2014-11 Impact factor: 3.437
Authors: Nathan D Seligson; Esko A Kautto; Edward N Passen; Colin Stets; Amanda E Toland; Sherri Z Millis; Christian F Meyer; John L Hays; James L Chen Journal: Oncologist Date: 2018-12-12
Authors: Krishnansu S Tewari; Michael W Sill; Harry J Long; Richard T Penson; Helen Huang; Lois M Ramondetta; Lisa M Landrum; Ana Oaknin; Thomas J Reid; Mario M Leitao; Helen E Michael; Bradley J Monk Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Robert L Coleman; Gini F Fleming; Mark F Brady; Elizabeth M Swisher; Karina D Steffensen; Michael Friedlander; Aikou Okamoto; Kathleen N Moore; Noa Efrat Ben-Baruch; Theresa L Werner; Noelle G Cloven; Ana Oaknin; Paul A DiSilvestro; Mark A Morgan; Joo-Hyun Nam; Charles A Leath; Shibani Nicum; Andrea R Hagemann; Ramey D Littell; David Cella; Sally Baron-Hay; Jesus Garcia-Donas; Mika Mizuno; Katherine Bell-McGuinn; Danielle M Sullivan; Bruce A Bach; Sudipta Bhattacharya; Christine K Ratajczak; Peter J Ansell; Minh H Dinh; Carol Aghajanian; Michael A Bookman Journal: N Engl J Med Date: 2019-09-28 Impact factor: 91.245
Authors: Joyce F Liu; William T Barry; Michael Birrer; Jung-Min Lee; Ronald J Buckanovich; Gini F Fleming; Bj Rimel; Mary K Buss; Sreenivasa Nattam; Jean Hurteau; Weixiu Luo; Philippa Quy; Christin Whalen; Lisa Obermayer; Hang Lee; Eric P Winer; Elise C Kohn; S Percy Ivy; Ursula A Matulonis Journal: Lancet Oncol Date: 2014-09-10 Impact factor: 41.316
Authors: X Bian; J Gao; F Luo; C Rui; T Zheng; D Wang; Y Wang; T M Roberts; P Liu; J J Zhao; H Cheng Journal: Oncogene Date: 2017-09-25 Impact factor: 9.867
Authors: Hannah Farmer; Nuala McCabe; Christopher J Lord; Andrew N J Tutt; Damian A Johnson; Tobias B Richardson; Manuela Santarosa; Krystyna J Dillon; Ian Hickson; Charlotte Knights; Niall M B Martin; Stephen P Jackson; Graeme C M Smith; Alan Ashworth Journal: Nature Date: 2005-04-14 Impact factor: 69.504